We propose to construct proof-of-concept prototype modules for a small animal nuclear imaging system, based on structured scintillator plates read out through wavelength-shifting optical fibers. Small animal nuclear imaging systems, and in particular small animal PET systems, are recently-developed systems which are finding a wide range of application in drug research and development. These animal imagers can directly provide quantitative knowledge of the movement and bioavailability of drugs (pharmacokinetics) and their therapeutic and toxic effects on living systems (pharmacodynamics). Current state-of-the-art small animal imaging systems have not yet reached fundamental limits in spatial resolution, have quite limited sensitivity and angular acceptance, and are extremely expensive. We will address each of these deficiencies, achieving extremely fine spatial resolution over an extended volume in a cost-effective manner amenable to large-acceptance and high-sensitivity systems. This will be achieved through the combination of two complementary novel technologies: structured scintillators to preserve system spatial resolution, and wavelength-shifting fiber readout for the cost- effective and high-resolution conversion of photonic to electronic event information. Phase II efforts will focus on the development of a complete small-animal nuclear imaging system as a prototype product. PROPOSED COMMERCIAL APPLICATIONS: Because drug development begins with animal research, small-animal PET imagers will allow studies to be performed on living animals early in the process of drug development and will make it possible to take advantage of advances in genetics to probe specific drug mechanisms in genetically altered living animals.